Linked Life Data

21237236

Source:http://linkedlifedata.com/resource/pubmed/id/21237236

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2011-2-14
pubmed:abstractText
Carcinogenesis is often linked to aberrant activation of Wnt/?-catenin signalling, in many cases caused by activating CTNNB1 mutations (encoding ?-catenin). Recently, ?-catenin was established as a decisive regulator of hepatic glutamine synthetase (GS) and cytochrome P450 (CYP) expression in mouse hepatocarcinogenesis. This study was aimed to analyse the connection of ?-catenin signalling and GS/CYP expression in human paediatric tumours. Samples from 23 paediatric tumours were analysed for activating mutations in CTNNB1. Protein expression of the model ?-catenin target GS and of various CYP isoforms was analysed and correlated with CTNNB1 mutational status and histological findings. Activating CTNNB1 mutations were frequent in hepatoblastoma (80%) and nephroblastoma (31%). In CTNNB1-mutated hepatoblastoma, expression of GS was only detected in tumour areas with epithelial, not with mesenchymal differentiation. Particularly high expression of glutamine synthetase was found in hepatoblastoma cells directly neighbouring a mesenchymal-type tumour area or stroma cells, associated with above-average cell proliferation. GS expression was not observed in CTNNB1-mutated nephroblastoma. Hepatoblastoma with activated ?-catenin expressed different CYPs relevant for the metabolism of cytostatic drugs, but with high interindividual variance and heterogeneity within a single tumour. GS and different CYPs are co-expressed in hepatoblastoma with activated ?-catenin. Moreover, other factors like histological subtype of tumour cells and cell-cell-interactions at the borders between different areas of the tumours affect expression of these ?-catenin target genes. Analysis of CYP expression in resected tumour tissue might be useful for the selection of appropriate cytostatics for post-operative chemotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1879-3185
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-14
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Differential expression of glutamine synthetase and cytochrome P450 isoforms in human hepatoblastoma.
pubmed:affiliation
Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tübingen, Wilhelmstr. 56, 72074 Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't